{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:25:40Z","timestamp":1791980740472,"version":"4.4.0"},"reference-count":147,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305775\/2024-3"],"award-info":[{"award-number":["305775\/2024-3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["EDITAL FAPERGS 09\/2023"],"award-info":[{"award-number":["EDITAL FAPERGS 09\/2023"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Dimethyl fumarate (DMF; C\n                    <jats:sub>6<\/jats:sub>\n                    H\n                    <jats:sub>8<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    ) is an ester of fumaric acid widely used in clinical practice for the treatment of relapsing forms of multiple sclerosis and plaque psoriasis. Beyond its established immunomodulatory actions, DMF is increasingly recognized as a small molecule capable of reshaping cellular redox homeostasis and mitochondrial physiology. Mitochondria are double-membrane organelles that integrate energy metabolism, calcium buffering, and apoptosis regulation, while also generating reactive oxygen species that function as signaling mediators. Given their central role in neuronal survival and function, mitochondrial integrity is a critical determinant of neuroprotection. The aim of this review is to discuss the mechanistic aspects by which DMF influences mitochondrial physiology in central nervous system (CNS) cells, based on evidence from experimental models and patient-derived samples. Data consistently show that DMF activates the Nrf2 pathway, leading to increased expression of antioxidant enzymes (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , NQO-1, HO-1) and induction of mitochondrial biogenesis markers (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , PGC-1\u03b1, NRF1, TFAM). In neurons and oligodendrocytes, DMF enhances respiratory function and limits apoptosis by modulating BCL-2 family proteins and suppressing cytochrome c release. Disease-relevant studies further demonstrate frataxin upregulation in Friedreich\u2019s ataxia and reduction of mitochondrial reactive oxygen species in C9orf72-related models. Conversely, in microglia, T cells, and vascular cells, DMF may impair mitochondrial respiration or increase apoptosis, particularly under inflammatory stress, suggesting a context-dependent effect. In conclusion, DMF exerts multifaceted and cell type\u2013specific actions on mitochondria. Understanding these mechanisms may guide optimized therapeutic strategies and the identification of biomarkers for precision use in neurological disorders.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1748360","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:01:26Z","timestamp":1770879686000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Marcos Roberto","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Grupo de Estudos em Neuroqu\u00edmica e Neurobiologia de Mol\u00e9culas Bioativas, Departamento de Qu\u00edmica, Universidade Federal de Mato Grosso (UFMT)","place":["Cuiaba, Mato Grosso, Brazil"]},{"name":"Grupo de Estudos em Terapia Mitocondrial, Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS)","place":["Porto Alegre, Rio Grande do Sul, Brazil"]},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Alimenta\u00e7\u00e3o, Nutri\u00e7\u00e3o e Sa\u00fade (PPGANS), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS)","place":["Porto Alegre, Rio Grande do Sul, Brazil"]},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas, Bioqu\u00edmica, Universidade Federal do Rio Grande do Sul (UFRGS)","place":["Porto Alegre, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"830650","DOI":"10.3389\/fmolb.2022.830650","article-title":"A drug combination rescues frataxin-dependent neural and cardiac pathophysiology in FA models","volume":"9","author":"Abeti","year":"2022","journal-title":"Front. 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